Heterogenicity of ornithine decarboxylase during mouse colon carcinogenesis and in human colon tumors.

Abstract

Ornithine decarboxylase (ODC) was separated, using diethylamino-ethyl ion-exchange chromatography, into multiple peaks of activity. We investigated the isoforms of ODC during 1,2-dimethylhydrazine-induced colon carcinogenesis and in human colon tumors. ODC in both mouse and human normal-appearing colonic mucosa was consistently separated into two active peaks by diethylaminoethyl-Sepharose CL-6B column chromatography. The major peak (Peak I) contained about 75% of the mouse and 72% of the human colonic mucosal ODC activity. During and after 10 weekly injections of 1,2-dimethylhydrazine (20 mg/kg, i.p.), colonic ODC activity was significantly enhanced with induction of both peaks but with a more significant increase in Peak II. ODC activity in both 1,2-dimethylhydrazine-induced and human colon tumors was significantly higher compared with the normal colon mucosa. The chromatographic profile of tumors showed the predominance of the second peak. Furthermore, the chromatographic profile of ODC after alkaline phosphatase treatment yielded an elution of only one peak coincident with the Peak I and the disappearance of Peak II. The second peak of ODC (the phosphorylated form) may be a specific isoform associated with colon tumorigenesis and tumor growth.